IP Library › Granted Patent US 9,006,195
Granted Patent B2
US 9,006,195 · App. 13/230,673 · Granted Apr 14, 2015

Regulation of hematopoietic stem cell functions through microRNAs

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Quick Facts
Patent No.
US 9,006,195
App. No.
13/230,673
Granted
Apr 14, 2015
Kind
B2
Abstract

The present disclosure relates to regulation of functions of hematopoietic stem cells (HSCs) by delivering of miRNAs, including miR-125b, miR-126, and miR-155, to HSCs. For example, in some embodiments, blood output in a mammal can be increased by administering miR-125b, miR-126, and/or miR-155 oligonucleotides. Also disclosed are methods for promoting hematopoietic stem cell engraftment and method for treating a myeloproliferative disorder.

Claims (17)

1. A method for increasing blood output in a mammal, comprising:

providing a mammal in need of increasing blood output; and

administering an oligonucleotide comprising a microRNA-125b (miR-125b) sequence to hematopoietic stem cells (HSCs) in the mammal, thereby increased blood output in the mammal, wherein the miR-125b sequence comprises a mature miR-125b1 sequence, a mature miR-125b2 sequence, a pre-miR-125b1 sequence, or a pre-miR-125b2 sequence.

2. The method of claim 1 , wherein the oligonucleotide comprises a nucleic acid sequence encoding a miR-125b selected from the group consisting of SEQ ID NOs: 1-3 and 5-6.

3. The method of claim 1 , wherein administering the oligonucleotide to the HSCs comprises contacting the HSCs with an expression construct comprising the oligonucleotide, thereby the miR-125b is expressed in the HSCs.

4. The method of claim 1 , further comprising measuring production of blood cells in the mammal.

5. The method of claim 4 , wherein the blood cells are selected from the group consisting of red blood cells, white blood cells, platelets, and any combination thereof.

6. The method of claim 4 , wherein measuring production of blood cells comprises measuring the number of the peripheral blood cells in the mammal.

7. The method of claim 1 , wherein the mammal suffers from low blood counts.

8. The method of claim 1 , wherein the mammal suffers from a disease or disorder selected from the group consisting of myelosuppression, pancytopenia, anemia, thrombocytopenia, leucopenia, neutropenia, and granulocytopenia.

9. A method for promoting hematopoietic stem cell engraftment in a mammal in need thereof, comprising:

administering an oligonucleotide comprising a microRNA-125b (miR-125b) sequence to hematopoietic stem cells (HSCs) in the mammal, wherein the miR-125b sequence is a mature miR-125b1 sequence, a mature miR-125b2 sequence, a pre-miR-125b1 sequence, or a pre-miR-125b2 sequence; and

measuring proliferation of B cells, T cells, or myeloid cells in the mammal.

10. The method of claim 9 , wherein the mammal suffers from low blood count, bone marrow failure disorders, or hematopoietic malignancies.

11. The method of claim 9 , wherein the mammal suffers from aplastic anemia.

12. The method of claim 9 , wherein administering the oligonucleotide to the HSCs comprises contacting the HSCs with an expression construct comprising oligonucleotide, thereby the miR-125b oligonucleotide is expressed in the HSCs.

13. The method of claim 9 , wherein the oligonucleotide comprises a nucleic acid sequence encoding a miR-125b selected from the group consisting of SEQ ID NOs: 1-3 and 5-6.